3. How can tobacco products and their ingredients be assessed?

3.1 What criteria for assessment should be used?

The assessment calls for measurement of the effects of additions to products which are already known to induce addiction. This means that assessment of additives needs to be against a baseline of addictive effects seen in their absence.

Human studies can use clinical criteria for dependence, such as compulsive tobacco use, loss of control over tobacco consumption, withdrawal symptoms upon the cessation of tobacco smoking, and relapse after periods of abstinence. Studies commonly measure tobacco dependence using criteria derived from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) used by doctors, a proxy measure for nicotine dependence based on answers to questions like “How soon after you wake do you light your first cigarette?, or simply by counting how many cigarettes a subject smokes each day. There are also laboratory measures of self-administration, smoking frequency and depth of inhalation of smoke, as well as preference for different products.

The situation is complicated by the fact that various studies indicate that tobacco products in general have higher addictive potential than pure nicotine. This is the result of a complex mixture of nicotine with other chemicals in tobacco smoke. At present it is impossible to evaluate whether additives increase the addictive potency of the final tobacco product.

In-depth investigation of effects of a variety of drugs on the brain indicates that an addict is someone who has a specific set of chronic conditions, related to a modification of regulation of neural networks. Strictly, the potential to induce these modifications should be the criterion which defines the addictive potency of a product.

Drugs of abuse such as nicotine induce different neurochemical and behavioural changes in animal studies. However, there is no consensus on which of these are directly related to addiction in humans.

The rewarding and reinforcing effects of nicotine, and development of nicotine tolerance and dependence, can be evaluated using animal models. These most often involve experimental set-ups in which animals can control their nicotine intake by self-administration of the drug. Most researchers consider these methods to be good models of human drug use, and to rely on the same neurobiological mechanisms. The simplest variants allow animals to take as much of a substance as they want, usually by mouth. More complex variants require the animal to behave in a certain way – a lever, for instance – to obtain a dose. The number of actions the animal, commonly a rat, must perform and the dosage rate can be varied to assess different regimes and their effects on addiction and reward.

There are further refinements of behavioural experiments involving pairing administration of the drug with an unconnected stimulus. As the animal becomes conditioned, its response to the stimulus may change, by being attracted to or repelled by a particular location, for example. This can be used for an indirect assessment of the effects of a drug or its withdrawal.

Experiments which allow animals to control electrical signals to small regions of the brain have been important for understanding the reward circuits of the brain. They can also be used to assess the way a drug may affect the reward circuits. If they are activated by administering the substance under test, the animal will seek lower electrical stimulation to maintain its level of reward.

There are no animal models at the moment for assessing the attractiveness of tobacco products.

Human studies rely on both subjective and objective effects of tobacco products. Subjective measures involve such reported effects as mood and craving and more elaborate questionnaire based assessments. There are a range of laboratory assessments of actual smoking behaviour. They measure things like the size of puffs, how long they take, and the intervals between them. And the effects of smoking can be monitored by neurological techniques which register various kinds of electrical activity in the brain.

Efforts to evaluate attractiveness in humans are often comparative, and may rely on panel studies or surveys of product preferences. When the additives in different products are known, these studies can provide information about the role of individual additives in the overall appeal of the product.

In principle, attractiveness can be tested experimentally, by measuring responses to tobacco products carefully formulated to include or exclude specific additives, and to vary the amounts. However, human testing of different tobacco products is ethically problematic, particularly if it involves non-users or children.

3.3 Are current methods adequate?

Limitations on the methods for assessing addictiveness stem from the fact that it is difficult to carry out systematic experiments in which specific additives are present or absent. Such experiments need hefty technical and financial input. Some have probably been done by the tobacco industry, especially on sugars and their derivatives. However, there are obvious ethical problems in testing additives for addictiveness on humans. For these reasons, current methods for testing whether additives enhance the addictiveness of tobacco are inadequate.

Assessing the indirect enhancement of addiction by increasing attractiveness also relies on human studies, some of which face ethical problems similar to those which arise when studying addictiveness in humans.